Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.
Nat Rev Endocrinol. 2024 Jul;20(7):399-413. doi: 10.1038/s41574-024-00969-x. Epub 2024 Mar 18.
Bone development and bone remodelling during adult life are highly anabolic processes requiring an adequate supply of oxygen and nutrients. Bone-forming osteoblasts and bone-resorbing osteoclasts interact closely to preserve bone mass and architecture and are often located close to blood vessels. Chondrocytes within the developing growth plate ensure that bone lengthening occurs before puberty, but these cells function in an avascular environment. With ageing, numerous bone marrow adipocytes appear, often with negative effects on bone properties. Many studies have now indicated that skeletal cells have specific metabolic profiles that correspond to the nutritional microenvironment and their stage-specific functions. These metabolic networks provide not only skeletal cells with sufficient energy, but also biosynthetic intermediates that are necessary for proliferation and extracellular matrix synthesis. Moreover, these metabolic pathways control redox homeostasis to avoid oxidative stress and safeguard cell survival. Finally, several intracellular metabolites regulate the activity of epigenetic enzymes and thus control the fate and function of skeletal cells. The metabolic profile of skeletal cells therefore not only reflects their cellular state, but can also drive cellular activity. Insight into skeletal cell metabolism will thus not only advance our understanding of skeletal development and homeostasis, but also of skeletal disorders, such as osteoarthritis, diabetic bone disease and bone malignancies.
在成年期，骨骼发育和骨重塑是高度合成代谢的过程，需要充足的氧气和营养供应。成骨细胞和破骨细胞密切相互作用以维持骨量和骨结构，它们通常靠近血管。发育中的生长板中的软骨细胞确保青春期前发生骨延长，但这些细胞在无血管环境中发挥作用。随着年龄的增长，大量骨髓脂肪细胞出现，这常常对骨特性产生负面影响。许多研究现在表明，骨骼细胞具有特定的代谢特征，与营养微环境及其特定阶段的功能相对应。这些代谢网络不仅为骨骼细胞提供了足够的能量，还提供了增殖和细胞外基质合成所需的生物合成中间体。此外，这些代谢途径控制氧化还原平衡以避免氧化应激并保证细胞存活。最后，几种细胞内代谢物调节表观遗传酶的活性，从而控制骨骼细胞的命运和功能。因此，骨骼细胞的代谢特征不仅反映了它们的细胞状态，而且可以驱动细胞活性。对骨骼细胞代谢的深入了解不仅将促进我们对骨骼发育和稳态的理解，而且还将促进对骨关节炎、糖尿病性骨病和骨恶性肿瘤等骨骼疾病的理解。
